G6PD deficiency in Indonesia: a systematic review and update of prevalence and variant maps in the context of malaria elimination

Abstract

Background: Low-daily-dose primaquine (PQ) (0·25 mg/kg/day over 14 days) remains the first-line treatment for P. vivax hypnozoites in Indonesia but can trigger haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Indonesia's malaria treatment guidelines do not require G6PD deficiency (G6PDd) screening prior to administering low-daily-dose PQ regimen, but future implementation of high-daily-dose PQ regimen (1 mg/kg/day over 7 days) will require G6PD screening. To date, no exhaustive assessment of G6PDd prevalence has been done in Indonesia.MethodsA systematic search of the literature was conducted (PROSPERO 2022 CRD42022368319). Studies meeting predefined criteria reporting G6PDd prevalence and genetic variants in Indonesia were identified in a systematic search and complemented with previously unpublished studies meeting the same criteria. The collected data are presented descriptively and geospatially mapped.FindingsA total of 45 studies published between 1964 and 2024 were included. The prevalences of G6PDd (<30% activity) were 0·0–19·9% across 87 sites (n = 23,166), and the prevalences of females with deficient and intermediate (30–70% activity) activities were 0·8–44·6% across 35 sites (n = 6729). G6PDd allele frequencies (males with <30% activity) were 0·0–25·9% across 82 sites (n = 10,680). Fifteen class B G6PD variants were reported, presenting oxidant-induced acute haemolytic anaemia. No relevant data were available for many areas of the country, including those with high P. vivax malaria incidences.InterpretationOur findings support the introduction of routine G6PDd screening to guide high-daily-dose PQ treatment. However, G6PDd prevalence is heterogeneous across Indonesia, and available information is not comprehensive. This is of concern in areas with high endemicity of P. vivax malaria, where treatment with PQ is required. This lack of data needs to be addressed to inform and guide appropriate routine G6PDd screening to support P. vivax malaria elimination targets.FundingThis work was supported, in whole or in part, by the Bill & Melinda Gates Foundation (INV-024389).